1. Field of the Invention
The present invention relates to antigenic noninfectious acquired immunological deficiency syndrome (AIDS) viruses (also referred to as human immunodeficiency virus, HIV), cloned human T cells producing the antigenic noninfectious HIV, and use of the antigenic noninfectious HIV and the cloned cells. Since the present HIV viruses are noninfectious but still antigenic, they can be used as safe and effective HIV antigen in the field of diagnosis, and therapy of AIDS. Moreover, since the present cloned T cells produce the antigenic HIV but do not form syncytia, the cells as such are promising for use as a safe live vaccine for the HIV.
2. Description of the Related Art
For the treatment of AIDS caused by the infection of human immunodeficiency virus (HIV), currently interleukins, interferons, azidothymidine (AZT) and the like are used, but these have not been fully evaluated, and in practice are not truly effective agents.
Accordingly, a vaccine therapy is now urgently sought as an effective prophylactic and therapeutic treatment method for AIDS. For vaccine therapy, it is essential to obtain an extremely safe antigen essential for the production of an antibody to HIV. At present, as a method of producing such an antigen, the use of transformed cells which are antigenic but noninfectious is under investigation. For example, Ikuta et al., Jpn. J. Cancer Res. (Gann), 79, 418-423, April 1988, reported a transformed cell line derived from a human T cell MT-4 line. But, the MT-4 cell line was originally derived from a cell infected with HTLV-1, which is an etiologic virus for adult T cell leukemia, and therefore, is per se pathogenic. Moreover, although the transformed cell derived from MT-4 produces noninfectious virions, since it has a syncytium forming ability, it is not practical as vaccine material. Note, the syncytium forming ability, in the present case, is an ability of a transformed cell to fuse with nomal T cells to form a multi-nuclear cell, resulting in the death of the cell.
Another approach to obtain an antibody to HIV is to genetically produce a protein fragment derived from HIV. This approach is not particularly desirable, as it is considered that the antigenic potency of the immunogenic protein fragment is weaker than that of whole HIV. Moreover, since whole HIV contains various antigens, it provides various antibodies to HIV and provides an extremely potent vaccine. An antigenic protein fragment does not have this advantage.
Regarding the diagnosis of AIDS, since it is reported that many cases of AIDS are caused by a transfusion of blood infected with HIV, sera from blood donors are screened by an enzyme-linked immunoadsorbent assay (ELISA), immuno blotting or agglutination test prior to use of the blood. These assay methods, however, require a purified virion or protein isolated from cells infected with HIV, as antigen to detect the antiserum to HIV. To prepare such a virus antigen, however, a large amount of infectious HIV or tissue culture product containing HIV (several hundred litters per week) must be processed, requiring operators to be continuously exposed to materials infected with HIV, and thus to be continually under a potential risk of infection by HIV.
Further, in this diagnosis of AIDS, even if the results of the above-mentioned assays are positive, this does not always mean that the subject has AIDS, and therefore, it is considered that a confirmatory diagnosis must be made. To make this confirmatory diagnosis, an indirect immunofluorescence technique is known whereby HIV-infected cells reacted with a serum sample taken from a patient, further reacted with a fluorescence-labeled second antibody, and the HIV-infected cells thus treated then microscopically observed. In this assay, where the serum sample of patient contains an antibody to the virus, the HIV-infected cell generates a fluorescence. Nevertheless, since this assay uses HIV-infected cells, the operator is still at risk of infection by HIV, and therefore, this technique is not widely used on a routine test.